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PDBsum entry 1kfv
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Hydrolase/DNA
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PDB id
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1kfv
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Contents |
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* Residue conservation analysis
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PDB id:
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Hydrolase/DNA
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Title:
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Crystal structure of lactococcus lactis formamido-pyrimidine DNA glycosylase (alias fpg or mutm) non covalently bound to an ap site containing DNA.
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Structure:
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5'-d( Cp Tp Cp Tp Tp Tp (Pdi)p Tp Tp Tp Cp Tp C)-3'. Chain: d, g. Engineered: yes. Other_details: contains a 1,3 propanediol site (pdi). 5'-d( Gp Ap Gp Ap Ap Ap Cp Ap Ap Ap Gp Ap G)-3'. Chain: e, h. Engineered: yes. Formamido-pyrimidine DNA glycosylase. Chain: a, b.
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Source:
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Synthetic: yes. Lactococcus lactis. Organism_taxid: 1358. Gene: mutm or fpg. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Trimer (from
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Resolution:
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2.55Å
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R-factor:
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0.251
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R-free:
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0.285
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Authors:
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L.Serre,K.Pereira De Jesus,S.Boiteux,C.Zelwer,B.Castaing
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Key ref:
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L.Serre
et al.
(2002).
Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA.
EMBO J,
21,
2854-2865.
PubMed id:
DOI:
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Date:
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23-Nov-01
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Release date:
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14-Jun-02
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PROCHECK
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Headers
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References
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P42371
(FPG_LACLC) -
Formamidopyrimidine-DNA glycosylase from Lactococcus lactis subsp. cremoris
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Seq:
Struc:
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273 a.a.
264 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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C-T-C-T-T-T-X-T-T-T-C-T-C
13 bases
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G-A-G-A-A-A-C-A-A-A-G-A-G
13 bases
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C-T-C-T-T-T-X-T-T-T-C-T-C
13 bases
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G-A-G-A-A-A-C-A-A-A-G-A-G
13 bases
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Enzyme class 1:
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E.C.3.2.2.23
- DNA-formamidopyrimidine glycosylase.
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Reaction:
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Hydrolysis of DNA containing ring-opened N(7)-methylguanine residues, releasing 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimide.
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Enzyme class 2:
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E.C.4.2.99.18
- DNA-(apurinic or apyrimidinic site) lyase.
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Reaction:
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2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H+
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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DOI no:
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EMBO J
21:2854-2865
(2002)
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PubMed id:
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Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase bound to an abasic site analogue-containing DNA.
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L.Serre,
K.Pereira de Jésus,
S.Boiteux,
C.Zelwer,
B.Castaing.
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ABSTRACT
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The formamidopyrimidine-DNA glycosylase (Fpg, MutM) is a bifunctional base
excision repair enzyme (DNA glycosylase/AP lyase) that removes a wide range of
oxidized purines, such as 8-oxoguanine and imidazole ring-opened purines, from
oxidatively damaged DNA. The structure of a non-covalent complex between the
Lactoccocus lactis Fpg and a 1,3-propanediol (Pr) abasic site
analogue-containing DNA has been solved. Through an asymmetric interaction along
the damaged strand and the intercalation of the triad (M75/R109/F111), Fpg
pushes out the Pr site from the DNA double helix, recognizing the cytosine
opposite the lesion and inducing a 60 degrees bend of the DNA. The specific
recognition of this cytosine provides some structural basis for understanding
the divergence between Fpg and its structural homologue endo nuclease VIII
towards their substrate specificities. In addition, the modelling of the
8-oxoguanine residue allows us to define an enzyme pocket that may accommodate
the extrahelical oxidized base.
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Selected figure(s)
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Figure 6.
Figure 6 Stereo view of Fpg contacts around the Pr abasic site
analogue. Hydrogen bonds are indicated by dashed lines. DNA
atoms are represented by orange ball-and-sticks, and mutagenesis
targeted amino acids are underlined (see text for details). The
figures were generated by Molscript (Kraulis et al., 1991) and
Raster3-D (Merritt and Murphy, 1994).
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Figure 8.
Figure 8 Recognition of the C20 opposite the Pr site by R109.
Stereo view showing the intercalation of the Fpg triad by the
minor groove and the pseudo-Watson−Crick interactions between
R109 and C20. Hydrogen bonds are indicated by dashed lines. The
atomic coordinates of the triad (M70/R99/F101) from the free
TtFpg have been superposed and are represented by green
ball-and-sticks. The figure was generated by Molscript (Kraulis
et al., 1991) and Raster3-D (Merritt and Murphy, 1994).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2002,
21,
2854-2865)
copyright 2002.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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Google scholar
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PubMed id
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Reference
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K.Imamura,
S.S.Wallace,
and
S.Doublié
(2009).
Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNA.
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J Biol Chem,
284,
26174-26183.
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PDB codes:
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K.L.Tibballs,
O.H.Ambur,
K.Alfsnes,
H.Homberset,
S.A.Frye,
T.Davidsen,
and
T.Tønjum
(2009).
Characterization of the meningococcal DNA glycosylase Fpg involved in base excision repair.
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BMC Microbiol,
9,
7.
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M.Banach,
and
I.Roterman
(2009).
Recognition of protein complexation based on hydrophobicity distribution.
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Bioinformation,
4,
98.
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P.A.van der Kemp,
M.de Padula,
G.Burguiere-Slezak,
H.D.Ulrich,
and
S.Boiteux
(2009).
PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae.
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Nucleic Acids Res,
37,
2549-2559.
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S.D.Kathe,
R.Barrantes-Reynolds,
P.Jaruga,
M.R.Newton,
C.J.Burrows,
V.Bandaru,
M.Dizdaroglu,
J.P.Bond,
and
S.S.Wallace
(2009).
Plant and fungal Fpg homologs are formamidopyrimidine DNA glycosylases but not 8-oxoguanine DNA glycosylases.
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DNA Repair (Amst),
8,
643-653.
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B.R.Bowman,
S.Lee,
S.Wang,
and
G.L.Verdine
(2008).
Structure of the E. coli DNA glycosylase AlkA bound to the ends of duplex DNA: a system for the structure determination of lesion-containing DNA.
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Structure,
16,
1166-1174.
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PDB codes:
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F.Coste,
M.Ober,
Y.V.Le Bihan,
M.A.Izquierdo,
N.Hervouet,
H.Mueller,
T.Carell,
and
B.Castaing
(2008).
Bacterial base excision repair enzyme Fpg recognizes bulky N7-substituted-FapydG lesion via unproductive binding mode.
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Chem Biol,
15,
706-717.
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PDB code:
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A.Banerjee,
W.L.Santos,
and
G.L.Verdine
(2006).
Structure of a DNA glycosylase searching for lesions.
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Science,
311,
1153-1157.
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PDB codes:
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C.Buré,
B.Castaing,
C.Lange,
and
A.F.Delmas
(2006).
Location and base selectivity on fragmentation of brominated oligodeoxynucleotides.
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J Mass Spectrom,
41,
84-90.
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M.Rogacheva,
A.Ishchenko,
M.Saparbaev,
S.Kuznetsova,
and
V.Ogryzko
(2006).
High resolution characterization of formamidopyrimidine-DNA glycosylase interaction with its substrate by chemical cross-linking and mass spectrometry using substrate analogs.
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J Biol Chem,
281,
32353-32365.
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R.K.Walker,
A.K.McCullough,
and
R.S.Lloyd
(2006).
Uncoupling of nucleotide flipping and DNA bending by the t4 pyrimidine dimer DNA glycosylase.
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Biochemistry,
45,
14192-14200.
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G.Golan,
D.O.Zharkov,
H.Feinberg,
A.S.Fernandes,
E.I.Zaika,
J.H.Kycia,
A.P.Grollman,
and
G.Shoham
(2005).
Structure of the uncomplexed DNA repair enzyme endonuclease VIII indicates significant interdomain flexibility.
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Nucleic Acids Res,
33,
5006-5016.
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PDB codes:
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J.R.Horton,
K.Liebert,
S.Hattman,
A.Jeltsch,
and
X.Cheng
(2005).
Transition from nonspecific to specific DNA interactions along the substrate-recognition pathway of dam methyltransferase.
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Cell,
121,
349-361.
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PDB codes:
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K.Pereira de Jésus,
L.Serre,
C.Zelwer,
and
B.Castaing
(2005).
Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA.
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Nucleic Acids Res,
33,
5936-5944.
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PDB codes:
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B.B.Hopkins,
and
N.O.Reich
(2004).
Simultaneous DNA binding, bending, and base flipping: evidence for a novel M.EcoRI methyltransferase-DNA complex.
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J Biol Chem,
279,
37049-37060.
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E.I.Zaika,
R.A.Perlow,
E.Matz,
S.Broyde,
R.Gilboa,
A.P.Grollman,
and
D.O.Zharkov
(2004).
Substrate discrimination by formamidopyrimidine-DNA glycosylase: a mutational analysis.
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J Biol Chem,
279,
4849-4861.
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F.Coste,
M.Ober,
T.Carell,
S.Boiteux,
C.Zelwer,
and
B.Castaing
(2004).
Structural basis for the recognition of the FapydG lesion (2,6-diamino-4-hydroxy-5-formamidopyrimidine) by formamidopyrimidine-DNA glycosylase.
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J Biol Chem,
279,
44074-44083.
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PDB codes:
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J.C.Fromme,
A.Banerjee,
and
G.L.Verdine
(2004).
DNA glycosylase recognition and catalysis.
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Curr Opin Struct Biol,
14,
43-49.
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L.Larivière,
and
S.Moréra
(2004).
Structural evidence of a passive base-flipping mechanism for beta-glucosyltransferase.
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J Biol Chem,
279,
34715-34720.
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PDB codes:
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M.de Padula,
G.Slezak,
P.Auffret van Der Kemp,
and
S.Boiteux
(2004).
The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae.
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Nucleic Acids Res,
32,
5003-5010.
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N.Gillard,
M.Begusova,
B.Castaing,
and
M.Spotheim-Maurizot
(2004).
Radiation affects binding of Fpg repair protein to an abasic site containing DNA.
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Radiat Res,
162,
566-571.
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P.Amara,
L.Serre,
B.Castaing,
and
A.Thomas
(2004).
Insights into the DNA repair process by the formamidopyrimidine-DNA glycosylase investigated by molecular dynamics.
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Protein Sci,
13,
2009-2021.
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S.Doublié,
V.Bandaru,
J.P.Bond,
and
S.S.Wallace
(2004).
The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activity.
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Proc Natl Acad Sci U S A,
101,
10284-10289.
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PDB code:
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V.V.Koval,
N.A.Kuznetsov,
D.O.Zharkov,
A.A.Ishchenko,
K.T.Douglas,
G.A.Nevinsky,
and
O.S.Fedorova
(2004).
Pre-steady-state kinetics shows differences in processing of various DNA lesions by Escherichia coli formamidopyrimidine-DNA glycosylase.
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Nucleic Acids Res,
32,
926-935.
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A.David,
N.Bleimling,
C.Beuck,
J.M.Lehn,
E.Weinhold,
and
M.P.Teulade-Fichou
(2003).
DNA mismatch-specific base flipping by a bisacridine macrocycle.
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Chembiochem,
4,
1326-1331.
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F.Barone,
E.Dogliotti,
L.Cellai,
C.Giordano,
M.Bjørås,
and
F.Mazzei
(2003).
Influence of DNA torsional rigidity on excision of 7,8-dihydro-8-oxo-2'-deoxyguanosine in the presence of opposing abasic sites by human OGG1 protein.
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Nucleic Acids Res,
31,
1897-1903.
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G.L.Verdine,
and
D.P.Norman
(2003).
Covalent trapping of protein-DNA complexes.
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Annu Rev Biochem,
72,
337-366.
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J.C.Fromme,
and
G.L.Verdine
(2003).
DNA lesion recognition by the bacterial repair enzyme MutM.
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J Biol Chem,
278,
51543-51548.
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PDB codes:
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K.D.Corbett,
and
J.M.Berger
(2003).
Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution.
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EMBO J,
22,
151-163.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
